Trial Outcomes & Findings for Valacyclovir for Mild Cognitive Impairment (NCT NCT04710030)
NCT ID: NCT04710030
Last Updated: 2026-03-31
Results Overview
18F-Florbetapir PET imaging is hypothesized to show amyloid accumulation in sum of six ROIs (cerebellar gray matter reference) that are known to show increased uptake in AD: medial orbital frontal, anterior cingulate, parietal, temporal, posterior cingulate, precuneus.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
50 participants
Primary outcome timeframe
Week 0 to Week 52
Results posted on
2026-03-31
Participant Flow
Participant milestones
| Measure |
Valacyclovir
Oral valacyclovir will be distributed in 500mg caplets. Patients will take 8 caplets per day (total dose: 4 grams per day) for 52 weeks.
Valacyclovir hydrochloride 500mg caplet: Active Comparator
|
Placebo
The oral placebo (sugar pill) will be distributed in 500mg caplets. Patients will take 8 caplets per day for 52 weeks.
Placebo sugar pill caplet: Placebo Comparator
|
|---|---|---|
|
Overall Study
STARTED
|
24
|
26
|
|
Overall Study
COMPLETED
|
22
|
20
|
|
Overall Study
NOT COMPLETED
|
2
|
6
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Valacyclovir for Mild Cognitive Impairment
Baseline characteristics by cohort
| Measure |
Valacyclovir
n=24 Participants
Oral valacyclovir will be distributed in 500mg caplets. Patients will take 8 caplets per day (total dose: 4 grams per day) for 52 weeks.
Valacyclovir hydrochloride 500mg caplet: Active Comparator
|
Placebo
n=26 Participants
The oral placebo (sugar pill) will be distributed in 500mg caplets. Patients will take 8 caplets per day for 52 weeks.
Placebo sugar pill caplet: Placebo Comparator
|
Total
n=50 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
69.3 years
STANDARD_DEVIATION 9.4 • n=4 Participants
|
68.4 years
STANDARD_DEVIATION 8.9 • n=28 Participants
|
68.9 years
STANDARD_DEVIATION 9.2 • n=10 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=4 Participants
|
14 Participants
n=28 Participants
|
28 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=4 Participants
|
12 Participants
n=28 Participants
|
22 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=4 Participants
|
5 Participants
n=28 Participants
|
8 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
21 Participants
n=4 Participants
|
21 Participants
n=28 Participants
|
42 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=4 Participants
|
0 Participants
n=28 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=4 Participants
|
1 Participants
n=28 Participants
|
1 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=4 Participants
|
0 Participants
n=28 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=4 Participants
|
0 Participants
n=28 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=4 Participants
|
9 Participants
n=28 Participants
|
15 Participants
n=10 Participants
|
|
Race (NIH/OMB)
White
|
14 Participants
n=4 Participants
|
14 Participants
n=28 Participants
|
28 Participants
n=10 Participants
|
|
Race (NIH/OMB)
More than one race
|
4 Participants
n=4 Participants
|
2 Participants
n=28 Participants
|
6 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=4 Participants
|
0 Participants
n=28 Participants
|
0 Participants
n=10 Participants
|
|
Region of Enrollment
United States
|
24 participants
n=4 Participants
|
26 participants
n=28 Participants
|
50 participants
n=10 Participants
|
|
Education in years
|
17.0 years
STANDARD_DEVIATION 3.9 • n=4 Participants
|
15.4 years
STANDARD_DEVIATION 3.2 • n=28 Participants
|
16.1 years
STANDARD_DEVIATION 3.6 • n=10 Participants
|
|
Apolipoprotein E e4 positive
|
11 Participants
n=4 Participants
|
14 Participants
n=28 Participants
|
25 Participants
n=10 Participants
|
|
PACC composite z-score
|
0.03 z-score
STANDARD_DEVIATION 0.74 • n=4 Participants
|
-0.03 z-score
STANDARD_DEVIATION 0.70 • n=28 Participants
|
0.0 z-score
STANDARD_DEVIATION 0.72 • n=10 Participants
|
|
ADCS-ADL-PI
|
40.55 units on a scale
STANDARD_DEVIATION 5.48 • n=4 Participants
|
40.89 units on a scale
STANDARD_DEVIATION 3.92 • n=28 Participants
|
40.72 units on a scale
STANDARD_DEVIATION 4.70 • n=10 Participants
|
|
CDR sum of boxes
|
1.29 units on a scale
STANDARD_DEVIATION 0.87 • n=4 Participants
|
1.44 units on a scale
STANDARD_DEVIATION 0.71 • n=28 Participants
|
1.37 units on a scale
STANDARD_DEVIATION 0.79 • n=10 Participants
|
|
MMSE
|
26.8 units on a scale
STANDARD_DEVIATION 1.4 • n=4 Participants
|
26.3 units on a scale
STANDARD_DEVIATION 1.7 • n=28 Participants
|
26.6 units on a scale
STANDARD_DEVIATION 1.6 • n=10 Participants
|
|
Ptau-217
|
0.47 pg/ml
STANDARD_DEVIATION 0.43 • n=4 Participants
|
0.50 pg/ml
STANDARD_DEVIATION 0.36 • n=28 Participants
|
0.49 pg/ml
STANDARD_DEVIATION 0.39 • n=10 Participants
|
|
18F-Florbetapir PET SUVR
|
1.30 SUV ratio
STANDARD_DEVIATION 0.14 • n=4 Participants
|
1.35 SUV ratio
STANDARD_DEVIATION 0.22 • n=28 Participants
|
1.33 SUV ratio
STANDARD_DEVIATION 0.18 • n=10 Participants
|
|
MRI hippocampal volume
|
3626 cubic mm
STANDARD_DEVIATION 505 • n=4 Participants
|
3711 cubic mm
STANDARD_DEVIATION 561 • n=28 Participants
|
3669 cubic mm
STANDARD_DEVIATION 533 • n=10 Participants
|
|
MRI cortical thickness
|
2.49 mm
STANDARD_DEVIATION 0.09 • n=4 Participants
|
2.49 mm
STANDARD_DEVIATION 0.12 • n=28 Participants
|
2.49 mm
STANDARD_DEVIATION 0.11 • n=10 Participants
|
PRIMARY outcome
Timeframe: Week 0 to Week 52Population: Eligible participants with mild cognitive impairment and seropositivity to herpes simplex virus 1 or 2 were randomized to receive valacyclovir 4 g/day (n=24) or matching placebo (n=26) for 52 weeks.
18F-Florbetapir PET imaging is hypothesized to show amyloid accumulation in sum of six ROIs (cerebellar gray matter reference) that are known to show increased uptake in AD: medial orbital frontal, anterior cingulate, parietal, temporal, posterior cingulate, precuneus.
Outcome measures
| Measure |
Valacyclovir
n=24 Participants
Oral valacyclovir will be distributed in 500mg caplets. Patients will take 8 caplets per day (total dose: 4 grams per day) for 52 weeks.
Valacyclovir hydrochloride 500mg caplet: Active Comparator
|
Placebo
n=26 Participants
The oral placebo (sugar pill) will be distributed in 500mg caplets. Patients will take 8 caplets per day for 52 weeks.
Placebo sugar pill caplet: Placebo Comparator
|
|---|---|---|
|
Change in Standardized Uptake Value Ratio (SUVR) of (18F-Florbetapir PET) From Week 0 to Week 52.
|
0.07 Standardized Uptake Value Ratio
Interval 0.0 to 0.14
|
0.08 Standardized Uptake Value Ratio
Interval 0.01 to 0.16
|
SECONDARY outcome
Timeframe: Assessed by Change in Least Square Means from Week 0 to Week 52 (measure in Outcome Measure Data Table), covarying for baseline score, age, sex and apolipoprotein E e4 status.Population: Eligible participants with mild cognitive impairment and seropositivity to herpes simplex virus 1 or 2 were randomized to receive valacyclovir or placebo.
The ADCS-PACC combines four paper-and-pencil cognitive tests: list-learning task from the Free and Cued Selective Reminding Test (FCSRT), paragraph recall test from the Wechsler Memory Scale, Digit Symbol Substitution Test and the Mini-Mental State Examination (MMSE). z-scores are generated from the combination of these test scores. The z-score range is from -5 to +5 with higher scores indicating less deficit and lower scores indicating greater deficit.
Outcome measures
| Measure |
Valacyclovir
n=24 Participants
Oral valacyclovir will be distributed in 500mg caplets. Patients will take 8 caplets per day (total dose: 4 grams per day) for 52 weeks.
Valacyclovir hydrochloride 500mg caplet: Active Comparator
|
Placebo
n=26 Participants
The oral placebo (sugar pill) will be distributed in 500mg caplets. Patients will take 8 caplets per day for 52 weeks.
Placebo sugar pill caplet: Placebo Comparator
|
|---|---|---|
|
Change From Week 0 to Week 52 in the Alzheimer's Disease Cooperative Study-Preclinical Alzheimer Cognitive Composite (PACC) Z-score
|
0.30 z-score
Interval 0.04 to 0.55
|
0.03 z-score
Interval -0.23 to 0.29
|
SECONDARY outcome
Timeframe: Assessed by Change in Least Square Means from Week 0 to Week 52 (measure in Outcome Measure Data Table), covarying for baseline score, age, sex and apolipoprotein E e4 status.Population: Eligible participants with mild cognitive impairment and seropositivity to herpes simplex virus 1 or 2 were randomized to receive valacyclovir or placebo.
The ADCS-ADL-PI will be administered to the informant for the assessment of impairments of instrumental and related activities of daily living in patients with MCI. The sum score of the first 15 items in the instrument that indicate impairments in function related to cognition is the outcome. Scores range from 0-45 with lower scores indicating greater functional deficit and higher scores indicating less functional deficit.
Outcome measures
| Measure |
Valacyclovir
n=24 Participants
Oral valacyclovir will be distributed in 500mg caplets. Patients will take 8 caplets per day (total dose: 4 grams per day) for 52 weeks.
Valacyclovir hydrochloride 500mg caplet: Active Comparator
|
Placebo
n=26 Participants
The oral placebo (sugar pill) will be distributed in 500mg caplets. Patients will take 8 caplets per day for 52 weeks.
Placebo sugar pill caplet: Placebo Comparator
|
|---|---|---|
|
Change From Week 0 to Week 52 in the Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale-Prevention Instrument (ADCS-ADL-PI)
|
1.65 units on a scale
Interval -0.05 to 3.34
|
-0.31 units on a scale
Interval -1.97 to 1.36
|
SECONDARY outcome
Timeframe: Assessed by Change in Least Square Means from Week 0 to Week 52 (measure in Outcome Measure Data Table), covarying for baseline score, age, sex and apolipoprotein E e4 status.Population: Eligible participants with mild cognitive impairment and seropositivity to herpes simplex virus 1 or 2 were randomized to receive valacyclovir or placebo.
The Clinical Dementia Rating is an assessment that evaluates and stages the severity of dementia by scoring a patient's cognitive and functional abilities in six domains. Each domain is rated from 0 (no impairment) to 3 (severe impairment). The total score ranges from 0 to 18 with 0 indicating no impairment and 18 indicating severe impairment.
Outcome measures
| Measure |
Valacyclovir
n=24 Participants
Oral valacyclovir will be distributed in 500mg caplets. Patients will take 8 caplets per day (total dose: 4 grams per day) for 52 weeks.
Valacyclovir hydrochloride 500mg caplet: Active Comparator
|
Placebo
n=26 Participants
The oral placebo (sugar pill) will be distributed in 500mg caplets. Patients will take 8 caplets per day for 52 weeks.
Placebo sugar pill caplet: Placebo Comparator
|
|---|---|---|
|
Change From Week 0 to Week 52 in Clinical Dementia Rating (CDR) Sum of Boxes
|
-0.17 units on a scale
Interval -0.7 to 0.36
|
0.22 units on a scale
Interval -0.32 to 0.76
|
Adverse Events
Valacyclovir
Serious events: 1 serious events
Other events: 18 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 21 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Valacyclovir
n=24 participants at risk
Oral valacyclovir will be distributed in 500mg caplets. Patients will take 8 caplets per day (total dose: 4 grams per day) for 52 weeks.
Valacyclovir hydrochloride 500mg caplet: Active Comparator
|
Placebo
n=26 participants at risk
The oral placebo (sugar pill) will be distributed in 500mg caplets. Patients will take 8 caplets per day for 52 weeks.
Placebo sugar pill caplet: Placebo Comparator
|
|---|---|---|
|
Metabolism and nutrition disorders
Fever
|
0.00%
0/24 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
3.8%
1/26 • Number of events 1 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
|
Gastrointestinal disorders
Gall bladder surgery
|
4.2%
1/24 • Number of events 1 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
0.00%
0/26 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
|
Cardiac disorders
Ablation for atrial fibrillation
|
4.2%
1/24 • Number of events 1 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
0.00%
0/26 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
|
Renal and urinary disorders
Hematuria
|
4.2%
1/24 • Number of events 1 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
0.00%
0/26 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
4.2%
1/24 • Number of events 1 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
0.00%
0/26 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
|
Vascular disorders
Syncope with hypertension
|
4.2%
1/24 • Number of events 1 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
3.8%
1/26 • Number of events 1 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
|
Musculoskeletal and connective tissue disorders
Lumbar fusion for back pain
|
0.00%
0/24 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
3.8%
1/26 • Number of events 1 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
Other adverse events
| Measure |
Valacyclovir
n=24 participants at risk
Oral valacyclovir will be distributed in 500mg caplets. Patients will take 8 caplets per day (total dose: 4 grams per day) for 52 weeks.
Valacyclovir hydrochloride 500mg caplet: Active Comparator
|
Placebo
n=26 participants at risk
The oral placebo (sugar pill) will be distributed in 500mg caplets. Patients will take 8 caplets per day for 52 weeks.
Placebo sugar pill caplet: Placebo Comparator
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
muscle pain
|
0.00%
0/24 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
15.4%
4/26 • Number of events 4 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
|
Renal and urinary disorders
elevated serum creatinine
|
8.3%
2/24 • Number of events 2 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
3.8%
1/26 • Number of events 1 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/24 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
7.7%
2/26 • Number of events 2 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
|
Gastrointestinal disorders
diarrhea
|
16.7%
4/24 • Number of events 4 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
11.5%
3/26 • Number of events 3 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
|
Nervous system disorders
dizziness
|
8.3%
2/24 • Number of events 2 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
7.7%
2/26 • Number of events 2 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
|
Nervous system disorders
confusion
|
0.00%
0/24 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
7.7%
2/26 • Number of events 2 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
|
General disorders
Fatigue
|
8.3%
2/24 • Number of events 2 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
11.5%
3/26 • Number of events 3 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
|
Nervous system disorders
headache
|
16.7%
4/24 • Number of events 4 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
3.8%
1/26 • Number of events 1 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
|
Respiratory, thoracic and mediastinal disorders
respiratory
|
8.3%
2/24 • Number of events 2 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
11.5%
3/26 • Number of events 3 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
|
Skin and subcutaneous tissue disorders
skin rash
|
8.3%
2/24 • Number of events 2 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
7.7%
2/26 • Number of events 2 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
|
Investigations
Abnormal lab results
|
8.3%
2/24 • Number of events 2 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
0.00%
0/26 • Adverse event data were collected for the 52 week (1 year) time period for each partticipant.
Frequency of adverse events reported by the participant during the trial was collected.
|
Additional Information
Dr. Davangere Devanand
New York State Psychiatric Institute
Phone: 646-774-8658
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place